The goal of this project is to study the mechanism of chemically-induced murine hepatomas, and to identify and characterize endogenous and exogenous factors that may control initiation, promotion and progression of these tumors. Topics of present interest are (1) isolation and characterization of preneoplastic liver cell populations; (2) characterization of transplantation and growth of normal, preneoplastic and neoplastic rat hepatocytes in the anterior chamber of the eye of the isogenic host; and (3) modulation of cell surface receptors during chemically-induced hepatoma formation in the rat. Results obtained so far include: (1) immunohistochemical studies using antibodies against the asialoglycoprotein surface receptor of normal rat hepatocytes have confirmed the lack of this receptor in preneoplastic areas in rat liver. The areas lacking the asialoglycoprotein receptor are entirely superimposable with glucose-6-phosphatase-deficient areas and partially overlapped with the gamma-glutamyltranspeptidase positive areas in serial liver sections. (2) Due to the lack of asialoglycoprotein receptor on the surface of preneoplatic hepatocytes, an efficient method for separation of these cells from noraml hepatocytes was developed using tissue culture plates coated with asialofetuin. Only normal cells attach, whereas preneoplastic and neoplastic cells do not. (3) In contrast to the reduction of asialoglycoprotein receptors during early stages of hepatocarcinogenesis, the surface recpetor protein for transferrin is present at an increased level. (4) The transplantation to the anterior chamber of the rat eye offers a promising model to study attachment and growth of normal, preneoplastic, neoplastic and in vitro carcinogen treated liver cells.